Synergistic antimicrobial and antibiofilm activities of piperic acid and 4-ethylpiperic acid amides in combination with ciprofloxacin

In the present work, piperic acid and 4-ethylpiperic acid (EPA) amides with amino acids ( C1–C8 ) were bio-evaluated for their antimicrobial activity and biofilm inhibition against Gram-positive and Gram-negative bacterial strains. Among all, EPA-β 3,3 -Pip(Bzl)-OMe, C2 displayed the potent antimicrobial activity with MIC of 6.25 μg ml –1 against Gram-negative bacteria Escherichia coli . In combination studies, the FIC indices suggested that C1 and C2 have a synergistic effect with ciprofloxacin against E. coli and Bacillus subtilis , whereas C5 exhibited a synergistic effect with ciprofloxacin against all the tested bacteria. The inhibitory effect of amides C1 , C2 , and C5 on the biofilm formation of test strains was significantly potentiated by co-administration with ciprofloxacin. Furthermore, the effective concentrations of C2 in combination reduced drastically compared to alone for biofilm inhibition. At these concentrations, C2 showed negligible hemolytic and cytotoxic activities.